Phenotypes associated with this allele

• Allele Symbol: Casp8^tm1Hed
• Allele Name: targeted mutation 1, Stephen M Hedrick
• Allele ID: MGI:3696985
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Casp8^tm1Hed/Casp8^tm1Hed Cd19^tm1(cre)Cgn/Cd19^+	involves: 129P2/OlaHsd	MGI:3697395
cn2	Casp8^tm1Hed/Casp8^tm1Hed Tg(KRT14-cre)1Efu/0	Not Specified	MGI:4888399

Genotype
MGI:3697395

cn1

• Allelic Composition: Casp8^tm1Hed/Casp8^tm1Hed; Cd19^tm1(cre)Cgn/Cd19⁺
• Genetic Background: involves: 129P2/OlaHsd

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

immune system

decreased B cell number ( J:116713 )

decreased B-1 B cell number ( J:116713 )

• modest reduction in B1 cells (~10%) in peritoneal cavity is seen

decreased marginal zone B cell number ( J:116713 )

• reduction in percentage of marginal zone B cells is observed

spleen hypoplasia ( J:116713 )

• spleen cell number is increased ~30% compared to wild-type

abnormal adaptive immunity ( J:116713 )

decreased B cell proliferation ( J:116713 )

• in response to LPS and dsRNA, B cells have decreased proliferative response

• cells stimulated through Tlr9 or antigen receptor show similar proliferation and apoptosis to wild-type cells

abnormal immunoglobulin level ( J:116713 )

• mice mount an inferior IgM response to LPS immunization

hematopoietic system

decreased B cell proliferation ( J:116713 )

• in response to LPS and dsRNA, B cells have decreased proliferative response

• cells stimulated through Tlr9 or antigen receptor show similar proliferation and apoptosis to wild-type cells

decreased B cell number ( J:116713 )

decreased B-1 B cell number ( J:116713 )

• modest reduction in B1 cells (~10%) in peritoneal cavity is seen

decreased marginal zone B cell number ( J:116713 )

• reduction in percentage of marginal zone B cells is observed

spleen hypoplasia ( J:116713 )

• spleen cell number is increased ~30% compared to wild-type

abnormal immunoglobulin level ( J:116713 )

• mice mount an inferior IgM response to LPS immunization

cellular

increased apoptosis ( J:116713 )

• cells treated with LPS or dsRNA show decreased survival (increased apoptosis) compared to controls at 24 hours, with decreased viability starting at 12 hours

• cells stimulated through Tlr9 or antigen receptor show similar proliferation and apoptosis to wild-type cells

decreased B cell proliferation ( J:116713 )

• in response to LPS and dsRNA, B cells have decreased proliferative response

• cells stimulated through Tlr9 or antigen receptor show similar proliferation and apoptosis to wild-type cells

Genotype
MGI:4888399

cn2

• Allelic Composition: Casp8^tm1Hed/Casp8^tm1Hed; Tg(KRT14-cre)1Efu/0
• Genetic Background: Not Specified

mortality/aging

premature death ( J:167299 )

• about 10% of mutants exhibit a mosaic skin phenotype and survive for months

postnatal lethality, incomplete penetrance ( J:167299 )

• about 90% of mutants die by P15, while 10% survive for months

integument

impaired skin barrier function ( J:167299 )

• mutants exhibit an increase in epidermal water loss

dermatitis ( J:167299 )

• mutants develop atopic dermatitis-like skin disease

• about 90% of mutants exhibit a uniform skin phenotype and die by P15 while mutants that survive longer than P15, exhibit the skin phenotype on the posterior region of the back skin

abnormal skin morphology ( J:167299 )

• 2.5-fold increase in the numbers of blood vessels in the skin as indicated by marker analysis

abnormal skin vasculature morphology ( J:167299 )

• 2.5-fold increase in the numbers of blood vessels in the skin as indicated by marker analysis

skin edema ( J:167299 )

• cutaneous edema is seen in the ears and feet

epidermal spongiosis ( J:167299 )

• affected skin of mutants surviving longer than P15 shows suprabasal cells with increased intracellular space, indicating development of spongiosis

abnormal epidermal layer morphology ( J:167299 )

• hyperproliferation of epithelial stem/progenitor cells in the skin

acanthosis ( J:167299 )

abnormal keratinocyte morphology ( J:167299 )

• the intracellular adhesion apparatus of the epidermis is disrupted, with keratinocytes showing an abnormal punctate localization of E-cadherin (Cdh1) due to increased shedding of E-cadherin

epidermal hyperplasia ( J:167299 )

• mutants exhibit epidermal hyperplasia

• topical application of clobetasol, a corticosteroid, substantially reduces the epidermal hyperplasia and abolishes the epidermal gaps

thick epidermis ( J:167299 )

dry skin ( J:167299 )

scaly skin ( J:167299 )

immune system

increased mast cell number ( J:167299 )

• mutants exhibit an increase in mast cells with age

increased IgE level ( J:167299 )

• IgE levels are normal in young mutants but adults show a 30-fold increase compared to wild-type mice

increased IgG1 level ( J:167299 )

• 5-fold increase in serum IgG1 levels in adults

abnormal T cell physiology ( J:167299 )

• marker analysis indicates that mutants exhibit a biphastic T-helper cell response, with a TH2 response during the acute phase of dermatitis followed by a TH1 response during the chronic phase of dermatitis

dermatitis ( J:167299 )

• mutants develop atopic dermatitis-like skin disease

• about 90% of mutants exhibit a uniform skin phenotype and die by P15 while mutants that survive longer than P15, exhibit the skin phenotype on the posterior region of the back skin

homeostasis/metabolism

skin edema ( J:167299 )

• cutaneous edema is seen in the ears and feet

epidermal spongiosis ( J:167299 )

• affected skin of mutants surviving longer than P15 shows suprabasal cells with increased intracellular space, indicating development of spongiosis

impaired skin barrier function ( J:167299 )

• mutants exhibit an increase in epidermal water loss

hematopoietic system

increased mast cell number ( J:167299 )

• mutants exhibit an increase in mast cells with age

increased IgE level ( J:167299 )

• IgE levels are normal in young mutants but adults show a 30-fold increase compared to wild-type mice

increased IgG1 level ( J:167299 )

• 5-fold increase in serum IgG1 levels in adults

abnormal T cell physiology ( J:167299 )

• marker analysis indicates that mutants exhibit a biphastic T-helper cell response, with a TH2 response during the acute phase of dermatitis followed by a TH1 response during the chronic phase of dermatitis

cardiovascular system

abnormal skin vasculature morphology ( J:167299 )

• 2.5-fold increase in the numbers of blood vessels in the skin as indicated by marker analysis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
atopic dermatitis		DOID:3310	OMIM:603165 OMIM:PS603165	J:167299